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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trial

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Science China Life Sciences 2025年第1期 249-262页

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Zhijie Wang Jie Wang Department of Oncology The Fifth Medical Center of Chinese PLA General Hospital Department of Thoracic Surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech cams key laboratory of Translational Research on Lung Cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences Department of Clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers,the non-squamous and squamous subtypes（nsqNSCLC and sqNSCLC） exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor（ICI）-based *** our inhouse training cohort（n=85）,the presence of the LRP1B deleterious mutation（LRP1B-del） was associated with longer and shorter progression-free survival（PFS） on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteraction<0.001).Multiplex immunofluorescence staining revealed an association between LRP1B-del and increased and decreased numbers of tumor-infiltrating CD8+T cells in nsqNSCLCs（P=0.040） and sqNSCLCs（P=0.014）,*** the POPLAR/OAK cohort,nsqNSCLCs with LRP1B-del demonstrated improved PFS benefits from atezolizumab over docetaxel(hazard ratio（HR）=0.70,P=0.046),whereas this benefit was negligible in those without LRP1B-del（HR=1.05,P=0.64）.Conversely,sqNSCLCs without LRP1B-del benefited more from atezolizumab（HR=0.60,P=0.002） than those with LRP1B-del（HR=1.30,P=0.31）.Consistent results were observed in the in-house CHOICE-01 cohort,in which nsqNSCLCs with LRP1B-del and sqNSCLCs without LRP1B-del benefited more from toripalimab plus chemotherapy than from chemotherapy alone(Pinteraction=0.008).This multi-cohort study delineates the antithetical impacts of LRP1B-del in nsqNSCLCs and sqNSCLCs on predicting the benefits from ICI alone or with chemotherapy over chemotherapy *** findings highlight the distinct clinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

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Wheat PROTON GRADIENT REGULATION 5 is Involved in Tolerance to Photoinhibition

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Journal of Integrative Agriculture 2014年第6期13卷 1206-1215页

作者： WANG Yuan-ge HE Xue MA Wen-ying ZHAO Xue-qiang LI Bin TONG Yi-ping The State key laboratory for Plant Cell and Chromosome Engineering Institute of Genetics and Developmental Biology Chinese Academy of Sciences

Wheat （Triticum aestivum L.） often experiences photoinhibition due to strong light during the grain filling stage. As such, increasing the tolerance of wheat to photoinhibition is very desirable in breeding efforts focused on increasing grain yields. Previous reports have suggested that PROTON GRADIENT REGULATION 5 （PGR5） plays a central role in the generation of a proton gradient across the thylakoid membrane （ApH） and in acclimation to high light intensity conditions. Three PGR5 homoeologues were isolated from wheat, and mapped onto chromosomes 7A, 7B and 7D, respectively. The TaPGR5s shared highly similar genomic sequences and gene structures. The transcripts of TaPGR5s were found to be abundantly expressed in the flag leaves, and were transiently up-regulated by treatment with high light. High light treatment inhibited the net photosynthetic rate （Pn） and the maximal quantum yield ofphotosystem II （Fv/Fm）. Further, these inhibitions were more evident in the leaves with reduced expression of TaPGR5s achieved using virus-induced gene silencing methods. Moreover, reducing TaPGR5 expression impaired the induction of non-photochemical quenching （NPQ）, which caused more severe cell membrane damage and lipid peroxidation in high light. Additionally, we observed that TaPGR5s transcripts were more abundantly expressed in the wheat genotypes with higher ms-delayed light emission （ms-DLE）, a value reflecting transthylakoid ApH. These results suggested that TaPGR5s play important roles in the tolerance of wheat to photoinhibition.

关键词： wheat TaPGR5 high light stress photoinhibition photosynthesis

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Genome-Wide Survey and Expression Analysis of P_(1B)-ATPases in Rice, Maize and Sorghum

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Rice science 2018年第4期25卷 208-217页

作者： E Zhiguo LI Tingting CHEN Chen WANG Lei key laboratory of Rice biology China National Rice Research Institute key laboratory of Plant Functional genomics Ministry of Education/Key Laboratory of Crop Genetics and Physiology of Jiangsu Province/College of Agriculture Yangzhou University

P1B-type ATPase ion pumps that transport heavy metal ions across cellular membranes are essential for plant growth and development. To date, a genomic comparison overview of the family in rice, maize and sorghum is not yet available. In this study, a total of 31 heavy metal P1B-type ATPase （HMA） genes were identified, including 9 in rice, 11 each from maize and sorghum. They were classified into two distinct subfamilies based on their sequence composition and phylogenetic relationship. Four pairs of HMA genes were expanded via gene duplication with tandemly duplicated. Comprehensive analyses were performed to investigate the expression profiles of HMA genes in various tissues by using quantitative real-time PCR. Some HMA members exhibited abundant and tissue-specific expression patterns. Moreover, most of the genes were found to be differentially expressed under the Cu/Cd treatment. This study will facilitate further studies on P1B-type ATPase family and provide valuable hints for the functional validation in rice, maize and sorghum.

关键词： P1B-type ATPase rice maize sorghum HMA gene family expression pattern analysis

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Genetic variations of glycinin subunit genes among cultivated and wild type soybean species

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Progress in Natural Science:Materials International 2008年第1期18卷 33-41页

作者： Chunmei Wang, Xiaolei Wu, Faxing Jia, Jinsong Zhang *, Shouyi Chen * National key laboratory of Plant genomics, Institute of genetics and Developmental biology, Chinese Academy of Sciences, Beijing 100101, China National key laboratory of Plant genomics Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing 100101 China

Glycinin is a predominant storage protein in most soybean accessions. It is a hexamer constituted by five major subunits, which can be classified into two groups. Group I contains G1, G2 and G3, and Group II contains G4 and G5. The genes encoding these subunits have been designated from Gy1 to Gy5, respectively. In the present study, Gy1 genomic fragments were cloned from wild accessions of sub- genera Glycine glycine, Glycine soja and a cultivar of Glycine max. Their sequences and the deduced amino acid sequences were com- pared. The residues critical for assembling of G1 subunits from the wild perennial accession were conservative. The Gy4 fragments were cloned from two wild perennial accessions and compared with that from subgenus Soja. The intron 3 of Gy4 had abundant vari- ations between the subgenera G. soja and G. glycine as well as within the subgenus G. glycine. Abundant variations existed in the dis- ordered regions 3 and 4 of G4 subunits from two wild perennial accessions. The genomic organization of glycinin genes was analyzed in 19 accessions from subgenera Soja and Glycine. The hybridization patterns were identical among the accessions of subgenus Soja. On the contrary, abundant polymorphisms existed between the accessions from subgenus Glycine. These results indicated that gly- cinin genes have high degree of conservation within subgenus Soja but more variations within subgenus Glycine.

关键词： Genetic variation Glycinin subunit genes Soybean

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EXPRESSION AND DELETION ANALYSIS OF EcoRII ENDONUCLEASE AND METHYLASE GENE

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Chinese Medical Sciences Journal 2001年第4期16卷 200-203页

作者：刘金毅赵晓娟孟雁沈洁薛越强史顺娣蔡有余 Department of genetics Institute of Laboratory Animal Science CAMS & PUMC Beijing 100021.

Objective. To clone complete EcoRII restriction endonuclease gene (ecoRIIR) and methyltransferase gene (ecoRIIM) in one vector and to analyze the coordinating expression of this whole R M ***. Unidirectional deletion subclones were constructed with ***/M genes were preliminarily located in the cloned fragment according to the enzyme activities of subclones. Exact deletion sites were determined by sequencing, and transcriptional start sites were determined by S1 mapping. Results. The DNA fragment which was cloned into pBluescript SK+contained intact ecoRIIR gene andecoRIIM gene, and two transcriptional start sites of ecoRIIR gene were determined. 132bp to 458bp from 3’end of ecoRIIR gene are indispensable to enzyme activities and deletion of 202bp from 3’end of ecoRIIM gene made enzyme lose the capability in DNA protection to resist specific cut with EcoRII endonuclease (EcoRII.R). Deletion of the coding and flanking sequences of one gene did not affect the expression of the other gene, and the recombinants only containing ecoRIIR gene appeared to be lethal to dcm+host. Conclusion. ecoRIIM gene linking closely to ecoRIIR gene is very important for the existence of the R M system in process of evolution, but the key tocontrol EcoRII R M order may not exist in transcriptional level .

关键词： EcoRII endonuclease EcoRII methylase deletion mutation gene expression

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Conditional and unconditional mapping of quantitative trait loci underlying plant height and tiller number in rice (Oryza sativa L.) grown at two nitrogen levels

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Progress in Natural Science:Materials International 2008年第12期18卷 1539-1547页

作者： Hua Jiang~(a,b) Liang Jiang~b Longbiao Guo~b Zhenyu Gao~b Dali Zeng~b Lihuang Zhu~c Guohua Liang~a Qian Qian~b a State key laboratory of Rice biology/key laboratory of Plant Functional Genomies,Ministry of Education of China,Yangzhou University,Yangzhou 225009,China b State key laboratory of Rice biology,China National Rice Research Institute,Hangzhou 310006,China c Institute of genetics,Chinese Academy of Sciences,Beijing 100101,China [a]State key laboratory of Rice biology/key laboratory of Plant Functional genomics Ministry of Education of China Yangzhou University Yangzhou 225009 China [b]State key laboratory of Rice biology China National Rice Research Institute Hangzhou 310006 China [c]Institute of genetics Chinese Academy of Sciences Beijing 100101 China

In this study,we used 127 double haploid (DH) lines to analyze agricultural traits of *** DH lines,derived from a ZYQ8 (indica)/JX17 (japonica) cross by anther culture,contained 160 RFLP and 83 SSR *** and conditional quantitative trait loci (QTL) mapping was conducted to analyze plant height (PH) and tillers per plant (TP) at five growth stages that were grown at two nitrogen *** PH and 13 TP unconditional QTL were identified in the different growth stages,including 19 QTL from high-nitrogen (HN) and 14 QTL from low-nitrogen (LN) *** conditional QTL for 14 genomic regions under LN/HN con- ditions showed that there was a significant effect on PH and TP across the different *** one conditional QTL,ph2-3,was unable to be detected in unconditional *** QTL were detected in the first four rice growth stages than in the final ***- more,a line from the DH mapping population,DH78,was identified in extreme phenotypes of PH and TP that exhibited dwarfism and less-tiller (dft) *** gene dft1 was mapped to chromosome 2 using a backcrossed population of DH78/JX17 through a map- based cloning *** location of dft1 coincided with the mapping region of the small-LOD peak,QTL ph2 and tp2,which were identified in plants grown in low-nitrogen *** backcrossing and fine-mapping successfully delimited the dft1 locus to a 91 kb region.

关键词： Oryza sativa Quantitative trait loci Double haploid (DH) population Developmental behavior Nitrogen Map-based cloning

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On the founder effect in COVID-19 outbreaks:how many infected travelers may have started them all?

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National Science Review 2021年第1期8卷 30-39页

作者： Yongsen Ruan Zhida Luo Xiaolu Tang Guanghao Li Haijun Wen Xionglei He Xuemei Lu Jian Lu Chung-I Wu State key laboratory of Biocontrol School of Life Sciences Sun Yat-sen University State key laboratory of Protein and Plant Gene Research Center for Bioinformatics School of Life SciencesPeking University CAS key laboratory of genomic and Precision Medicine Beijing Institute of Genomics Chinese Academy of Sciences State key laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyCenter for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

How many incoming travelers（I;at time 0, equivalent to the ‘founders’ in evolutionary genetics） infected with SARS-CoV-2 who visit or return to a region could have started the epidemic of that region? I;would be informative about the initiation and progression of epidemics. To obtain I;, we analyze the genetic divergence among viral populations of different regions. By applying the ‘individual-output’ model of genetic drift to the SARS-CoV-2 diversities, we obtain I; 0） or the fitness of the variants. With such a tiny trickle of human movement igniting many outbreaks, the crucial stage of repressing an epidemic in any region should,therefore, be the very first sign of local contagion when positive cases first become identifiable. The implications of the highly ‘portable’ epidemics, including their early evolution prior to any outbreak, are explored in the companion study（Ruan et al., personal communication）.

关键词： SARS-CoV-2 COVID-19 population genetics genetic drift founder effect

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Sequence-based Functional Metagenomics Reveals Novel Natural Diversity of Functional CopA in Environmental Microbiomes

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genomics, Proteomics & Bioinformatics 2023年第6期21卷 1182-1194页

作者： Wenjun Li Likun Wang Xiaofang Li Xin Zheng Michael F.Cohen Yong-Xin Liu Hebei key laboratory of Soil Ecology Centre for Agricultural Resources ResearchInstitute of Genetics and Developmental BiologyChinese Academy of SciencesShijiazhuang 050022China University of Chinese Academy of Sciences Beijing 100049China Department of biology Sonoma State UniversityRohnert ParkCA 94928USA State key laboratory of Plant genomics Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Exploring the natural diversity of functional genes/proteins from environmental DNA in high throughput remains *** this study,we developed a sequence-based functional metagenomics procedure for mining the diversity of copper(Cu)resistance gene copA in global microbiomes,by combining the metagenomic assembly technology,local BLAST,evolutionary trace analysis(ETA),chemical synthesis,and conventional functional *** total,87 metagenomes were collected from a public database and subjected to copA detection,resulting in 93,899 *** curation of 1214 hits of high confidence led to the retrieval of 517 unique CopA candidates,which were further subjected to ***,175 novel copA sequences of high quality were *** analysis showed that almost all these putative CopA proteins were distantly related to known CopA proteins,with 55 sequences from totally unknown *** novel and three known copA genes were chemically synthesized for further functional genomic tests using the Cu-sensitive Escherichia coli(DcopA).The growth test and Cu uptake determination showed that five novel clones had positive effects on host Cu resistance and *** recombinant harboring copA-like 15(copAL15)successfully restored Cu resistance of the host with a substantially enhanced Cu *** novel copA genes were fused with the gfp gene and expressed in *** for microscopic *** results showed that they were successfully expressed and their proteins were localized to the *** results here greatly expand the diversity of known CopA proteins,and the sequence-based procedure developed overcomes biases in length,screening methods,and abundance of conventional functional metagenomics.

关键词： Functional metagenomics Natural diversity CopA Evolutionary trace analysis Cu resistance

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Comparative genetic mapping revealed powdery mildew resistance gene MlWE4 derived from wild emmer is located in same genomic region of Pm36 and Ml3D232 on chromosome 5BL

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Journal of Integrative Agriculture 2015年第4期14卷 603-609页

作者： ZHANG Dong OUYANG Shu-hong WANG Li-li CUI Yu WU Qiu-hong LIANG Yong WANG Zhen-zhong XIE Jing-zhong ZHANG De-yun WANG Yong CHEN Yong-xing LIU Zhi-yong State key laboratory for Agrobiotechnology/Beijing key laboratory of Crop Genetic Improvement/key laboratory of Crop Heterosis Research & Utilization Department of Plant Genetics & BreedingChina Agricultural University

Powdery mildew, caused by Blumeria graminis f. sp. tritici, is one of the most devastating wheat diseases. Wild emmer wheat（Triticum turgidum ssp. dicoccoides） is a promising source of disease resistance for wheat. A powdery mildew resistance gene conferring resistance to B. graminis f. sp. tritici isolate E09, originating from wild emmer wheat, has been transferred into the hexaploid wheat line WE4 through crossing and backcrossing. Genetic analyses indicated that the powdery mildew resistance was controlled by a single dominant gene, temporarily designated Ml WE4. By mean of comparative genomics and bulked segregant analysis, a genetic linkage map of Ml WE4 was constructed, and Ml WE4 was mapped on the distal region of chromosome arm 5BL. Comparative genetic linkage maps showed that genes Ml WE4, Pm36 and Ml3D232 were co-segregated with markers XBD37670 and XBD37680, indicating they are likely the same gene or alleles in the same locus. The co-segregated markers provide a starting point for chromosome landing and map-based cloning of Ml WE4, Pm36 and Ml3D232.

关键词： wild emmer powdery mildew resistance gene Pm36 comparative genomics

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Identification of SSRs and differentially expressed genes in twocultivars of celery (Apium graveolens L.) by deep transcriptomesequencing

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Horticulture Research 2014年第1期1卷 272-280页

作者： Meng-Yao Li Feng Wang Qian Jiang Jing Ma Ai-Sheng Xiong State key laboratory of Crop genetics and Germplasm Enhancement Key Laboratory of Biology and Germplasm Enhancement of Horticultural Crops in East China of Ministry of AgricultureCollege of HorticultureNanjing Agricultural UniversityNanjing 210095China

Celery(Apium graveolens L.)is one of the most important and widely grown vegetables in the Apiaceae *** to the lack of comprehensive genomic resources,research on celery has mainly utilized physiological and biochemical approaches,rather than molecular biology,to study this *** sequencing has become an efficient and economic technology for obtaining information on gene expression that can greatly facilitate molecular and genomic studies of species for which a sequenced genome is not *** the present study,15893516 and 19818161 high-quality sequences were obtained by RNA-seq from two celery varieties‘Ventura’and‘Jinnan Shiqin’,*** obtained reads were assembled into 39584 and 41740 unigenes with mean lengths of 683 bp and 690 bp,respectively.A total of 1939 simple sequence repeat(SSR)markers were identified in‘Ventura’and 2004 SSRs in‘Jinnan Shiqin’.Di-nucleotide repeats were the most common repeat motif,accounting for 55.49%and 54.84%in‘Ventura’and‘Jinnan Shiqin’,respectively.A comparison of expressed genes between the two libraries,identified 338 differentially expressed genes(DEGs).Three hundred and three of the DEGs were annotated based on a sequence similarity search utilizing eight public ***,the expression profile of eight annotated DEGs was characterized in response to abiotic *** collective data generated in the present research represent a valuable resource for further genetic and molecular studies in celery.

关键词： collective utilizing utilized

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